Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model 英文参考文献.docVIP

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Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model 英文参考文献.doc

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Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model 英文参考文献

Moreauetal.ArthritisResearchTherapy2011,13:R98 /content/13/3/R98 RESEARCH ARTICLE OpenAccess Tiludronatetreatmentimprovesstructural changesandsymptomsofosteoarthritisinthe canineanteriorcruciateligamentmodel MaximMoreau1,2,PascaleRialland1,Jean-PierrePelletier2,JohanneMartel-Pelletier2,DanielLajeunesse2, ChristelleBoileau2,JudithCaron2,DianeFrank1,BertrandLussier1,JeromeREdelCastillo1,GuyBeauchamp1, DominiqueGauvin1,2,ThierryBertaim3,DominiqueThibaud4andEricTroncy1,2* Abstract Introduction:Theaimofthisprospective,randomized,controlled,double-blindstudywastoevaluatetheeffects oftiludronate(TLN),abisphosphonate,onstructural,biochemicalandmolecularchangesandfunctioninan experimentaldogmodelofosteoarthritis(OA). Methods:Baselinevalueswereestablishedtheweekprecedingsurgicaltransectionoftherightcranial/anterior cruciateligament,witheightdogsservingasOAplacebocontrolsandeightothersreceivingfourTLNinjections (2mg/kgsubcutaneously)attwo-weekintervalsstartingthedayofsurgeryforeightweeks.Atbaseline,Week4 andWeek8,thefunctionaloutcomewasevaluatedusingkineticgaitanalysis,telemeteredlocomotoractimetry andvideo-automatedbehaviourcapture.Painimpairmentwasassessedusingacompositenumericalratingscale (NRS),avisualanalogscale,andelectrodermalactivity(EDA).Atnecropsy(Week8),macroscopicand histomorphologicalanalysesofsynovium,cartilageandsubchondralboneofthefemoralcondylesandtibial plateauswereassessed.Immunohistochemistryofcartilage(matrixmetalloproteinase(MMP)-1,MMP-13,anda disintegrinandmetalloproteinasedomainwiththrombospondinmotifs(ADAMTS5))andsubchondralbone (cathepsinK)wasperformed.Synovialfluidwasanalyzedforinflammatory(PGE andnitrite/nitratelevels) 2 biomarkers.Statisticalanalyses(mixedandgeneralizedlinearmodels)wereperformedwithana-thresholdof0.05. Results:AbetterfunctionaloutcomewasobservedinTLNdogsthanOAplacebocontrols.Hence,TLNdogshad lowergaitdisability(P=0.04atWeek8)andNRSscore(P=0.03,groupeffect),anddemonstratedbehavioursof painlessconditionwiththevideo-capture(P